THE METHOD OF MODELLING OF EXPERIMENTAL THIOACETAMIDE LIVER DAMAGE IN RATS
Abstract
Background. The methods used in modelling of toxic liver damage are not always suitable for cirrhosis modelling, due to high mortality rate of experimental animals and poorly reproducible biochemical and morphological manifestations. Objective – to elaborate an experimental model of liver damage in rats, describe morphological changes in the liver as well as biochemical parameters revealing free radical processes and the state of antioxidant protection system in blood plasma of rats after prolonged administration of thioacetamide (ТАА). Material and methods. Rat liver damage was produced by TAA administration (200 mg/kg every other day, for 1 and for 3 months). The liver was subject to histological examination (hematoxylin-eosin and Mallory staining). The following biochemical parameters of blood plasma were determined: the activity of catalase, the content of malonic dialdehyde, diene/triene conjugates, and ceruloplasmin. Results. Long administration of TAA for 1 month induced the morphological picture of toxic hepatitis, for 3 months - the micronodular liver cirrhosis characterized by pronounced fibrosis with rearrangement of lobular structure of the liver. Cirrhosis was also accompanied by changes in indices of free radical processes and antioxidant protection. Conclusions. 3-month intake of ТАА in the dose of 200 mg/kg every other day can be used for the reproduction of liver cirrhosis in rats. The latter is accompanied by elevation of plasma content of diene/triene conjugates and the activity of catalase, decrease of the level of ceruloplasmin, the malonic dialdehyde level being unchanged.References
1.Skuratov AG, Lyzikov AN, Voropaev EV, Achinovich SL, Osipov BB. Jeksperimentalnoe modelirovanie toksicheskogo povrezhdenija pecheni [Experimental modeling of toxic hepatic injury]. Problemy zdorovja i jekologii. 2011;4(30):27-33. (Russian).
2. Osipov BB, Lyzikov AN, Skuratov AG, Prizentsov AA. Toksiko-alimentarnaja model’ cirroza pecheni u krys [Toxicalimentary model of liver cirrhosis in rats]. Problemy zdorovja i jekologii. 2018;1(55):62-66. (Russian).
3. Shea SM, Manseau EJ. Experimental toxic cirrhosis in the rats. Kinetics of hepatocyte proliferation during intermittent thioacetamide intoxication. Am. J. Pathol. 1968;52(1):55-68.
4. Shirin H, Sharvit E, Aeed H, Gavish D, Bruck R. Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats. World Journal of Gastroenterology. 2013;19(2):241-248. https://doi.org/10.3748/wjg.v19.i2.241.
5. Bhakuni GS, Bedi O, Bariwal J, Deshmukh R, Kumar P. Animal models of hepatotoxicity. Inflamm. Res. 2016;65(1):13-24. https://doi.org/10.1007/s00011-015-0883-0.
6. French SW, Miyamoto K, Tsukamoto H. Ethanol-induced hepatic fibrosis in the rat: role of the amount of dietary fat. Alcohol Clin. Exp. Res. 1986;10:135-195. https://doi.org/10.1111/j.1530-0277.1986.tb05175.x.
7. Muriel P, Ramos-Tovar E, Montes-Páez G, Buendía-Montaño LD. Experimental models of liver damage mediated by oxidative stress. In: Muriel P, editor. Liver Pathophysiology. Therapies and Antioxidants. 1 st. ed. Mexico: Academic press; 2017. p. 529-546.
8. Debnath S, Ghosh S, Hazra B. Inhibitory effect of Nymphaea pubescens Willd: flower extract on carrageenan-induced inflammation and CCl4-induced hepatotoxicity in rats. Food Chem. Toxicol. 2013;59:485-491. https://doi.org/10.1016/j.fct.2013.06.036.
9. Berger LM, Bhatt H, Combes B, Estabrook RW. CCl4-induced toxicity in isolated hepatocytes: the importance of direct solvent injury. Hepatology. 1986;6:36-45. https://doi.org/10.1002/hep.1840060108.
10. Lebedeva EI. Dinamika i polovye razlichija biohimicheskih izmenenij v syvorotke krovi pri jeksperimentalnom toksicheskom cirroze. Vestnik Vitebskogo gosudarstvennogo medicinskogo universiteta [Vestnik of Vitebsk State Medical University]. 2014;13(5):23-31. (Russian).
11. Mahiliavets EV, Garelik PV, Zimatkin SM, Anufrik SS, Prokopchik NI. Morfologija pecheni pri CCl4-inducirovannom cirroze pod vlijaniem fotodinamicheskoj terapii [Liver morphology at the CCl4-induced cirrhosis under the influence of photodynamic therapy]. Problemy zdorovja i jekologii. 2015;1(43):71-75. (Russian).
12. Liu Y, Meyer C, Xu C, Weng H, Hellerbrand C, ten Dijke P, Dooley S. Animal models of chronic liver diseases. Am. J. Physiol. Gastrointest. Liver Physiol. 2013;304(5):G449-G468. https://doi.org/10.1152/ajpgi.00199.2012.
13. Liedtke Ch, Luedde T, Sauerbruch T, Scholten D, Streetz K, Tacke F, Tolba R, Trautwein C, Trebicka J, Weiskirchen R. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6(1):Art. 19. https://doi.org/10.1186/1755-1536-6-19.
14. Tsukamoto H, Horne W, Kamimura S, Niemela O, Parkkila S, Yla-Herttuala S, Brittenham GM. Experimental liver cirrhosis induced by alcohol and iron. J. Clin. Invest. 1995;1:620-630. https://doi.org/10.1172/JCI118077.
15. French SW. How to prevent alcoholic liver disease. Exp. Mol. Pathol. 2015;98(2):304-307. https://doi.org/10.1016/j.yexmp.2015.03.007.
16. Kulbekov EF, Kulbekova JuE. Gepatoprotektornoe dejstvie timalina i suspenzii krasnogo kostnogo mozga pri jeksperimentalnom toksicheskom gepatite u krys [Hepatoprotective action of thymalinum and suspension of red bone marrow in treating experimental toxic hepatitis of rats]. Farmacija i farmakologija. 2014;5(6):24-28. https://doi.org/10.19163/2307-9266-2014-2-5(6)-24-28. (Russian).
17. Osikov MV, Makarova EA. Patofiziologicheskie aspekty modelirovanija ostroj pechenochnoj nedostatochnosti [Pathophysiologic aspects of acute liver failure modeling]. Vestnik Juzhno-Uralskogo gosudarstvennogo universiteta [Bulletin of South Ural State University]. 2010;6(182):105-110. (Russian).
18. Li XI, Benjamin S, Alexander B. Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality J. Hepatol. 2002;36(4):488-493. https://doi.org/10.1016/s0168-8278(02)00011-9.
19. Wallace MC, Hamesch K, Lunova M, Kim Y, Weiskirchen R, Strnad P, Friedman SL. Standard operating procedures in experimental liver research: thioacetamide model in mice and rats. Lab. Anim. 2015;49(1):21-29. https://doi.org/10.1177/0023677215573040.
20. Dashti H, Jeppsson B, Hägerstrand I. Hultberg B, Srinivas U, Abdulla M, Bengmark S. Thioacetamide- and carbon tetrachloride-induced liver cirrhosis. Eur. Surg. Res. 1989;21:83-91. https://doi.org/10.1159/000129007.
21. Müller A, Machnik F, Zimmermann T, Schubert H. Thioacetamide-induced cirrhosis-like liver lesions in rats –usefulness and reliability of this animal model. Exp. Pathol. 1988;34(1):229-236. https://doi.org/10.1016/s0232-1513(88)80155-5.
22. Munoz Torres E, Paz Bouza JI, López Bravo A, Abad Hernández MM, Carrascal Marino E. Experimental thioacetamide-induced cirrhosis of the liver. Histol. Histopathol. 1991;6(1):95-100.
23. Kabiri N, Setorki M, Darabi MA. Protective effects of Kombucha tea and silimarin against thioacetamide induced hepatic injuries in Wistar rats. World Appl. Sci. J. 2013;27(4):524-532. https://doi.org/10.5829/idosi.wasj.2013.27.04.38.
24. Zhang F, Ni Y, Yuan Y, Yin W, Gao Y. Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model. Science China Life Sciences. 2018;61(11):1369-1381. https://doi.org/10.1007/s11427-017-9268-y.
25. Wallace MC, Hamesch K, Lunova M, Kim Y, Weiskirchen R, Strnad P, Friedman SL. Standard operating procedures in experimental liver research: thioacetamide model in mice and rats. Lab. Anim. 2015;49(1):21-29. https://doi.org/10.1177/0023677215573040.
26. Volkova OV, Eleckij JuK. Osnovy gistologii s gistologicheskoj tehnikoj. 2nd ed. Moskva: Medicina; 1982. 304 p. (Russian).
27. Volchegorskij IA, Nalimov AG, Jarovinskiy BG, Lifshits RI.Sopostavlenie razlichnyh podhodov k opredeleniju produktov POL v geptan-izopropanolnyh jekstraktah krovi. Voprosy medicinskoj himii. 1989;35(1):127-131. (Russian).
28. Kamyshnikov VS. Spravochnik po kliniko-biohimicheskoj laboratornoj diagnostike. Vol. 1. Minsk: Interpresservis; 2003. 495 p. (Russian).
29. Koroljuk MA, Ivanova LI, Majorova IT. Metod opredelenija aktivnosti katalazy. Laboratornoe delo. 1988;1:16-19. (Russian).
